Visible response reveals promise as biomarker in autism-linked situation | Spectrum
See variants: The activity in the visual areas of the brain could reflect the genetics that underlie Phelan-Mcdermid syndrome.
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According to a new study, brain responses to visual stimuli in children with Phelan-McDermid syndrome, a genetic disorder associated with autism, are smaller and weaker than in non-autistic children. The difference in response is greater in children with larger genetic mutations.
Mutations or deletions in SHANK3, one of the genes most closely linked to autism, cause Phelan-McDermid syndrome. More than 80 percent of people with this disorder have autism; They also often have intellectual disabilities, developmental delays, and other medical problems, although these characteristics and their severity can vary widely.
The new study is the first to use electroencephalography (EEG) to measure visual evoked potentials – brain responses that occur shortly after a person sees a visual stimulus – in people with Phelan-McDermid syndrome. The team previously identified differences in these responses in people with “idiopathic” autism or autism with no known genetic cause. Other researchers have linked atypical visual evoked potentials to other single gene causes of autism such as Rett syndrome.
“Contributions like the one in this article, which allow us to have very clearly quantifiable biomarkers, are extremely valuable,” said Luigi Boccuto, assistant research scientist and director of the Phelan-McDermid Syndrome Research Program at Clemson University in Clemson, South Carolina not involved in the work. “They allow us to really categorize and better study and research the clinical features.”
The researchers measured brain activity in 175 children aged 20 months to 12 years – 31 with Phelan-McDermid and 20 of their unaffected siblings, and 79 with idiopathic autism and 45 without autism – while the children watched the color change on a chessboard for 60 seconds .
Children with Phelan-McDermid syndrome and idiopathic autism showed similar responses that were less than those of the unaffected siblings and the non-autistic children.
A shorter version of the test, consisting of 10 two-second trials, gave similar results and allowed more children to participate.
“[This] provides flexibility in collecting objective EEG biomarker data in populations where such data has been difficult to obtain in the past, ”says lead researcher Paige Siper, chief psychologist at the Seaver Autism Center at Mount Sinai Hospital in New York.
All children with Phelan-McDermid who had deletions in SHANK3 instead of mutations also had greatly reduced brain responses, the researchers found; those with larger deletions had the most reduced responses or no response. In contrast, some children with only point mutations – changes to a single “letter” of DNA – had more typical brain responses.
The results suggest that additional genes may interact with SHANK3 and affect how the disease is presented, says Boccuto. “They can do more damage than losing SHANK3 alone. The breakthrough is that we can quantify that to make a better forecast. “
The results were published in July in the Journal of the American Academy of Child and Adolescent Psychiatry.
Because brain responses in children with different forms of autism overlapped, future therapies effective for Phelan-McDermid syndrome could potentially help other autistic children with similar neural patterns, Siper says.
And visual evoked potentials could be a useful tool for measuring the effects of future therapies, says Boccuto.
“The goal, of course, is to develop a treatment that can fix these problems to some extent,” he says. “You can now measure the success of the treatment.”
Biomarkers have been especially difficult to identify in Phelan-McDermid syndrome, says Jimmy Lloyd Holder Jr., an uninitiated assistant professor of pediatrics, neurology, and developmental neuroscience at Baylor College of Medicine in Houston, Texas. This is in part because many people with the condition also have intellectual disabilities, which can make it difficult for them to participate in some data-gathering processes, such as functional magnetic resonance imaging.
“Really, before that there was very little for Phelan-McDermid syndrome,” says Holder.
EEG is easier to do and doesn’t require the sedation commonly used in brain imaging, Holder says, which makes this a promising technique. Many children with Phelan-McDermid have already done EEGs to monitor seizure activity.
Future work should involve a control group with idiopathic intellectual disabilities, Holder says, and examine whether evoked potentials are associated with certain behavioral traits.
Siper’s team is evaluating the use of visual evoked potentials in clinical trials of children with Phelan-McDermid and examining whether they are an effective biomarker in other genetic disorders associated with autism.